Systematically predict the transcriptomic switches required
to produce any target cell type from any source cell type.
The MOGRIFY® technology was developed as a systematic means of identifying the key regulatory switches, such as an optimal combination of transcription factors, required to drive cell identity. The platform can be used to enhance existing stem-cell forward reprogramming methods or can bypass development pathways altogether, affecting a direct trans-differentiation between a mature cell type to another mature cell type.
The platform follows a step-wise scientific approach to driving cell identity. Firstly, the RNA of the source and target cell types is sequenced in order to compare the gene expression levels in the context of all other possible cell types. Simultaneously, local transcriptomic regulatory networks are built around each regulatory gene in the human genome to calculate and rank the effect of the genes on the desired cell conversion by querying large-scale regulatory networks. The optimal combination of key regulators is predicted to maximize network coverage while avoiding redundancies. Once this optimal combination has been identified, the DNA sequence of each regulatory gene is encoded into delivery vectors, which are transduced into the source cell type causing changes in DNA expression profile and therefore switching the genetic programs of the cell which induces the conversion between source and target cell type.
In addition to identifying transcription factor-driven cell reprogramming, small molecules that are able to affect the expression of the key predicted transcription factors can be identified to create a small molecule reprogramming cocktail. This approach has the added benefit of not requiring the transduction of transcription factors and consequently holds greater potential as an in vivo reprogramming therapy.